Targeting Anticipatory Neurogenesis to Maintain Cognitive Reserve

Abstract Memory imprecision is a hallmark of age-related cognitive decline and mild-cognitive impairment (MCI) and is characterized by increased memory interference and decreased stability of memory representations. Evidence from humans, non-human primates and rodents demonstrate reduced hippocampal neurogenesis, excitation-inhibition imbalance and inflexible hippocampal remapping during age-related cognitive decline and MCI. Developing strategies to reverse cognitive decline during aging and Mild Cognitive Impairment necessitates an understanding of molecular, cellular, circuit and network mechanisms that support memory functions of the hippocampus. Over the last decade we have built a multifaceted program grounded in basic neuroscience that is aimed at improving memory in aging and MCI. We have demonstrated how we can Rejuvenate the aged hippocampus by selectively increasing neurogenesis and how we can Re-engineer connectivity of aged inhibitory microcircuits to improve memory precision in aging. Ongoing efforts include strategies to Repairing neurogenic niche fitness by targeting intercellular communication in the aging hippocampus. In today’s talk I will present a fourth approach catalyzed by our discovery of the first transcriptional regulator of neural stem cell expansion in the adult hippocampus. We will present data in support of this claim and convey how this discovery may guide strategies to maintain cognitive reserve embodied in the pool of neural stem cells in the adult hippocampus.


THE DEVASTATING ECONOMIC IMPACT OF COVID-19 ON OLDER BLACK AND LATINX ADULTS: IMPLICATIONS FOR HEALTH AND WELL-BEING Catherine Garcia, University of Nebraska -Lincoln, Lincoln, Nebraska, United States
The ongoing COVID-19 pandemic and subsequent economic recession have wreaked havoc on the United States' economy and brought to the forefront stark racial and ethnic inequalities in our society. Older Black and Latinx adults are particularly hard hit by the pandemic as they have relatively lower levels of income and wealth to protect against crises. This study used data from the 2020 COVID-19 module of the Health and Retirement Study, to highlight how the COVID-19 pandemic has economically impacted older Black, U.S.-born Latinx and foreign-born Latinx adults. Results show the pandemic has economically devastated older Black and Latinx adults across a host of economic factors, with foreign-born Latinx experiencing greater economic hardships relative to other groups. Our findings document stark inequalities that are being exacerbated by the pandemic. We discuss the implications of the economic shocks of the pandemic for the health and well-being of older Black and Latinx adults.

SYSTEMIC MECHANISMS OF BRAIN REJUVENATION Saul Villeda, University of California San Francisco
Aging drives cellular and cognitive impairments in the adult brain. It is imperative to gain mechanistic insight into what drives aging phenotypes in the brain in order to maintain, and even restore, functional integrity in the elderly. We, and others, have shown that systemic manipulations -such as heterochronic parabiosis (in which a young and old circulatory system are joined) and administration of young blood or exercise induced blood factors -can reverse age-related impairments in regenerative, synaptic and inflammatory processes, as well as rescue cognitive faculties in the aged brain. These studies have revealed an age-dependent bi-directionality in the influence of the systemic environment indicating pro-youthful factors in young blood elicit rejuvenation while pro-aging factors in old blood drive aging. It has been proposed that introducing pro-youthful factors or mitigating the effect of pro-aging factors may provide effective strategies to rejuvenate aging phenotypes in the brain. Despite this potential, much is unknown as to the systemic and molecular mechanisms regulating pro-youthful and pro-aging effects of blood-borne factors. I will discuss work from my research group that begins to provide mechanistic insight into the systemic and molecular drivers promoting rejuvenation in the aging brain. Memory imprecision is a hallmark of age-related cognitive decline and mild-cognitive impairment (MCI) and is characterized by increased memory interference and decreased stability of memory representations. Evidence from humans, non-human primates and rodents demonstrate reduced hippocampal neurogenesis, excitation-inhibition imbalance and inflexible hippocampal remapping during age-related cognitive decline and MCI. Developing strategies to reverse cognitive decline during aging and Mild Cognitive Impairment necessitates an understanding of molecular, cellular, circuit and network mechanisms that support memory functions of the hippocampus. Over the last decade we have built a multifaceted program grounded in basic neuroscience that is aimed at improving memory in aging and MCI. We have demonstrated how we can Rejuvenate the aged hippocampus by selectively increasing neurogenesis and how we can Re-engineer connectivity of aged inhibitory microcircuits to improve memory precision in aging. Ongoing efforts include strategies to Repairing neurogenic niche fitness by targeting intercellular communication in the aging hippocampus. In today's talk I will present a fourth approach catalyzed by our discovery of the first transcriptional regulator of neural stem cell expansion in the adult hippocampus. We will present data in support of this claim and convey how this discovery may guide strategies to maintain cognitive reserve embodied in the pool of neural stem cells in the adult hippocampus.

HOW TO PUBLISH: GUIDANCE FROM GSA'S JOURNAL EDITORS Chair: Suzanne Meeks
Each year he GSA publications team sponsors a symposium to assist authors who wish to publish in GSA's high impact and influential journals. The first part of the session will include five brief presentations from the editors of The Gerontologist, Innovation and Aging, and the Journals of Gerontology Series A and B plus GSA's managing editors. We will integrate practical tips with principles of publication ethics and scholarly integrity. The topics will be as follows: (1) Preparing your manuscript: strong and ethical scholarly writing for multidisciplinary audiences, (2) common problems that affect peer review, (3) addressing translational significance and fit to journal expectations, (4) transparency, documentation, and Open Science; and (5) working with Scholar One. Following these presentations, we will hold round table discussions with editors from the GSA journals portfolio. At these round tables, editors will answer questions related to the podium presentations and other questions specific to each journal. Intended audiences include emerging and international scholars, and authors interested in learning more about best practices and tips for getting their scholarly work published.

PREPARING YOUR MANUSCRIPT: STRONG AND ETHICAL SCHOLARLY WRITING FOR MULTIDISCIPLINARY AUDIENCES Suzanne Meeks, University of Louisville, Louisville, Kentucky, United States
This presentation will emphasize the importance of plain, good writing. Editors read 10 or more manuscripts per week with pressure to reject 80-90% of them. If the point and contribution are not clear in a quick scan of the paper, it will not be reviewed favorably. I will provide tips for writing that are commonly violated in submissions, provide references for additional writing support, cover expectations for language consistent with GSA's Reframing Aging initiative, and discuss some common publication ethics issues that arise during the review process, including author contributions and embedding your scholarship in the context of prior work.

COMMON PROBLEMS THAT IMPACT PEER REVIEW Rozalyn Anderson, University of Wisconsin College of Medicine, University of Wisconsin, Madison, Wisconsin, United States
This presentation will review the most common issues that affect how reviewers see a manuscript submission. These include clarity, use of figures, and attention to existing research, especially establishing the significance and novelty of the work, and how to frame a narrative. I will also address responding to peer review. The focus will be on the biological science perspective (Journals of Gerontology Series A), but these issues are relevant to all submissions to GSA journals.

DEFINING TRANSLATIONAL SIGNIFICANCE IN GERONTOLOGY Steven Albert, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
Innovation in Aging requires a statement from authors on translational significance. This requirement forces authors to consider the implications of their research for changing some component of aging. How does the research address a challenge posed by aging bodies, minds, relationships, or societies? The editorial board has developed criteria for assessing translational significance. Translational research must meet at least one of three criteria. It (i) must predict or explain a health or behavioral outcome, (ii) be advanced enough in deployment or development to assess these effects, and (iii) have a clear pathway to large-scale program delivery or change in clinical practice. The criteria rule out some kinds of submissions, such as scale development, single-case studies, or reviews of literature. We use these criteria to structure each article's required translational significance statement. Rethinking translation may help focus research across the full set of GSA journals.

TRANSPARENCY, DOCUMENTATION, AND OPEN SCIENCE
Derek Isaacowitz, Northeastern University, Northeastern University, Massachusetts, United States Some GSA journals are especially interested in promoting transparency and open science practices, reflecting how some subdisciplines in aging are moving toward open science practices faster than others. In this talk, I will consider the transparency and open science practices that seem most relevant to aging researchers, such as preregistration, open data, open materials and code, sample size justification and analytic tools for considering null effects. I will also discuss potential challenges to implementing these practices as well as reasons why it is important to do so despite these challenges. The focus will be on pragmatic suggestions for researchers